We propose to investigate several closely interrelated research issues in human cerebrovascular disease, using emission-tomographic strategies and short-lived radiolabeled tracer substances (chiefly (15)0-water, (15)O-oxygen, and (11)C-carbon monoxide) to characterize local metabolism and hemodynamics. (1) Patients with asymptomatic extracranial carotid artery lesions are studied to determine the hemodynamic impediment associated with graded stenosis. The chief hypothesis is that diameter stenoses above 75% induce local hemodynamic alterations, consisting initially of increased local blood volume (lCBV) with normal blood flow (lCBF), and that decreased local oxygen utilization (lCMR02) correlates with severe vascular stenosis or occlusion. (2) Patients with recent transient cerebral ischemic attacks are studied to define the frequency and extent of residual postischemic impairments of lCBF and lCMRO2. Standardized sensorimotor activation tasks are employed to determine whether the post-TIA state is associated with impaired hemodynamic and metabolic activation as compared to age-matched non-TIA controls. (3) We intend to assess the capability of emission tomography in monitoring responsiveness to acutely administered therapeutic agents by studying patients with recent completed thromboembolic infarction before and after acute hemodilution with low molecular weight dextran. We seek to determine whether this treatment improves local flow and oxygen extraction in and adjacent to the ischemic focus. (4) A sequential dual-tracer technique is used to quantitate local blood-brain barrier permeability to diffusion-limited radiotracers (such as (11)C-antipyrine) in patients with recent completed thromboembolic hemispheric strokes; barrier alterations are correlated with local flow patterns and with computed-tomographic appearances of infarct and adema in central and marginal zones of cerebral infarcts of different ages. (5) Concurrently, we propose to implement and validate a mathematical strategy for the simultaneous determination of local blood flow and local brain:brain partition coefficient. In addition, we propose to improve the existing mathematical model of oxygen extraction fraction by reformulating the model in terms of linear differential equations amenable to solution by the technique of dynamic approximation, and by explicitly incorporating radioactive decay.